Neonatal melanocortin receptor agonist treatment reduces play fighting and promotes adult attachment in prairie voles in a sex-dependent manner

Neuropharmacology. 2014 Oct;85:357-66. doi: 10.1016/j.neuropharm.2014.05.041. Epub 2014 Jun 9.


The melanocortin receptor (MCR) system has been studied extensively for its role in feeding and sexual behavior, but effects on social behavior have received little attention. α-MSH interacts with neural systems involved in sociality, including oxytocin, dopamine, and opioid systems. Acute melanotan-II (MTII), an MC3/4R agonist, potentiates brain oxytocin (OT) release and facilitates OT-dependent partner preference formation in socially monogamous prairie voles. Here we examined the long-term impact of early-life MCR stimulation on hypothalamic neuronal activity and social development in prairie voles. Male and female voles were given daily subcutaneous injections of 10 mg/kg MTII or saline between postnatal days (PND) 1-7. Neonatally-treated males displayed a reduction in initiated play fighting bouts as juveniles compared to control males. Neonatal exposure to MTII facilitated partner preference formation in adult females, but not males, after a brief cohabitation with an opposite-sex partner. Acute MTII injection elicited a significant burst of the immediate early gene EGR-1 immunoreactivity in hypothalamic OT, vasopressin, and corticotrophin releasing factor neurons, when tested in PND 6-7 animals. Daily neonatal treatment with 1 mg/kg of a more selective, brain penetrant MC4R agonist, PF44687, promoted adult partner preferences in both females and males compared with vehicle controls. Thus, developmental exposure to MCR agonists lead to a persistent change in social behavior, suggestive of structural or functional changes in the neural circuits involved in the formation of social relationships.

Keywords: Early experience; Melanocortin receptor; Melanotan-II; Oxytocin; Prairie voles; Social behavior.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aggression / drug effects*
  • Aggression / physiology
  • Animals
  • Animals, Newborn
  • Arvicolinae
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Early Growth Response Protein 1 / metabolism
  • Female
  • Hypothalamus / drug effects*
  • Hypothalamus / growth & development
  • Hypothalamus / physiology
  • Male
  • Neurons / drug effects
  • Neurons / physiology
  • Pair Bond*
  • Peptides, Cyclic / pharmacology
  • Play and Playthings
  • Psychotropic Drugs / pharmacology*
  • Random Allocation
  • Receptor, Melanocortin, Type 3 / agonists*
  • Receptor, Melanocortin, Type 3 / metabolism
  • Receptor, Melanocortin, Type 4 / agonists*
  • Receptor, Melanocortin, Type 4 / metabolism
  • Sex Characteristics*
  • alpha-MSH / analogs & derivatives
  • alpha-MSH / pharmacology


  • Early Growth Response Protein 1
  • Peptides, Cyclic
  • Psychotropic Drugs
  • Receptor, Melanocortin, Type 3
  • Receptor, Melanocortin, Type 4
  • melanotan-II
  • alpha-MSH